PYIH_MAGGR
ID PYIH_MAGGR Reviewed; 245 AA.
AC A0A4P8W851;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Short-chain dehydrogenase/reductase pyiH {ECO:0000303|PubMed:31099577};
DE EC=1.1.1.- {ECO:0000305|PubMed:31099577};
DE AltName: Full=Pyrichalasin H biosynthesis cluster protein H {ECO:0000303|PubMed:31099577};
GN Name=pyiH {ECO:0000303|PubMed:31099577};
OS Magnaporthe grisea (Crabgrass-specific blast fungus) (Pyricularia grisea).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Magnaporthales; Pyriculariaceae; Pyricularia.
OX NCBI_TaxID=148305;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=NI980;
RX PubMed=31099577; DOI=10.1021/acs.orglett.9b01344;
RA Wang C., Hantke V., Cox R.J., Skellam E.;
RT "Targeted gene inactivations expose silent cytochalasans in Magnaporthe
RT grisea NI980.";
RL Org. Lett. 21:4163-4167(2019).
RN [2]
RP FUNCTION.
RX PubMed=31644300; DOI=10.1021/acs.orglett.9b03372;
RA Wang C., Becker K., Pfuetze S., Kuhnert E., Stadler M., Cox R.J.,
RA Skellam E.;
RT "Investigating the function of cryptic cytochalasan cytochrome P450
RT monooxygenases using combinatorial biosynthesis.";
RL Org. Lett. 21:8756-8760(2019).
RN [3]
RP FUNCTION.
RX PubMed=32039410; DOI=10.1039/c9cc09590j;
RA Hantke V., Skellam E.J., Cox R.J.;
RT "Evidence for enzyme catalysed intramolecular [4+2] Diels-Alder cyclization
RT during the biosynthesis of pyrichalasin H.";
RL Chem. Commun. (Camb.) 56:2925-2928(2020).
CC -!- FUNCTION: Short-chain dehydrogenase/reductase; part of the gene cluster
CC that mediates the biosynthesis of the mycotoxin pyrichalasin H, a
CC tyrosine-derived cytochalasan that inhibits the growth of rice
CC seedlings, but also inhibits lymphocyte capping and actin
CC polymerization and alters cell morphology (PubMed:31099577) (Probable).
CC Pyrichalasin H is indicated as the responsible agent for the genus-
CC specific pathogenicity of M.grisea toward crabgrass (PubMed:31099577).
CC The first step in the pathway is catalyzed by the O-methyltransferase
CC pyiA which methylates free tyrosine to generate the precursor O-
CC methyltyrosine (PubMed:31099577). The hybrid PKS-NRPS pyiS, assisted by
CC the enoyl reductase pyiC, are responsible for fusion of the O-
CC methyltyrosine precursor and the polyketide backbone (PubMed:31099577).
CC The polyketide synthase module (PKS) of pyiS is responsible for the
CC synthesis of the polyketide backbone and the downstream nonribosomal
CC peptide synthetase (NRPS) amidates the carboxyl end of the polyketide
CC with the O-methyltyrosine precursor (PubMed:31099577). As the NRPS A-
CC domain demonstrates substrate tolerance, pyiS can also use
CC phenylalanine, tyrosine and even para-chlorophenylalanine as amino acid
CC precursor, which leads to the production of novel cytochalasans,
CC including halogenated cytochalasans (PubMed:31099577). Because pyiS
CC lacks a designated enoylreductase (ER) domain, the required activity is
CC provided the enoyl reductase pyiC (PubMed:31099577). Reduction by the
CC hydrolyase pyiE leads to 1,5-dihydropyrrolone, which is substrate for
CC dehydration and intra-molecular Diels-Alder cyclization by the Diels-
CC Alderase pyiF to yield the required isoindolone-fused macrocycle
CC (PubMed:32039410). The tailoring cytochrome P450 monooxygenases piyD
CC and piyG catalyze the hydroxylation at C-18 and C-7, respectivily,
CC whereas the short-chain dehydrogenase/reductase pyiH reduces the
CC carbonyl at C-21 in preparation for the transfer of an acetyl group by
CC the acetyltransferase pyiB (PubMed:31099577). These 3 reactions whose
CC order is not clear yet, lead to the production of O-methylpyrichalasin
CC J, a deacetylated pyrichalasin H (PubMed:31099577). Finally, pyiB to
CC converts O-methylpyrichalasin J into the final product pyrichalasin H
CC via acetylation of C-21 (PubMed:31099577).
CC {ECO:0000269|PubMed:31099577, ECO:0000269|PubMed:32039410,
CC ECO:0000305|PubMed:31644300}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:31099577}.
CC -!- DISRUPTION PHENOTYPE: Leads to the loss of pyrichalasin H production,
CC but accumulates novel cytochalasans. {ECO:0000269|PubMed:31099577}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; MK801691; QCS37520.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A4P8W851; -.
DR SMR; A0A4P8W851; -.
DR Proteomes; UP000515153; Genome assembly.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 3: Inferred from homology;
KW NAD; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..245
FT /note="Short-chain dehydrogenase/reductase pyiH"
FT /id="PRO_0000449454"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 10..18
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 36..37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 91..93
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 179..183
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 205..207
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 245 AA; 26790 MW; CDDB94E68DDBAEEC CRC64;
MPNLQGRVAF VTGGNAGIGY HTVVFLAKAG AKVYFGARSA SRAEAAVERM YRENPGLLHG
QVNWLQVDMA SMKSVLAGCD KFRASESKLN ILIHNAAHEG REPSNMADSG VQITMQTNHL
AVFAMTQELQ PMLRTAAAEK DSDVRIVNVS SNAPSLTHSD EWRPDFSDPH GGDIRYPAGQ
ADGFLAAMKR YSVSKMAMNL LTAELQARYD REGVPIMVIS VCPGAVYFKP QVDTENVEEM
MRQPT
